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1.
J Phys Chem Lett ; : 6063-6067, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32635727

RESUMO

Two-photon-excited fluorescence spectroscopy is a powerful tool to study the structural and electronic properties of optically active complexes and molecules. Although numerous lanthanide complexes have been characterized by two-photon-excited fluorescence in solution, this report is the first to apply such a technique to actinide compounds. Contrasting with previous observations in lanthanides, we demonstrate that the two-photon absorption properties of the complexes significantly depend on the metal (4f vs 5f), with Cm(III) complexes showing significantly higher two-photon absorption cross sections than lanthanide analogues and up to 200-fold stronger emission intensities. These results are consistent with electronic and structural differences between the lanthanide and actinide systems studied. Hence, the described methodology can provide valuable insights into the interactions between f-elements and ligands, along with promising prospects on the characterization of scarce compounds.

2.
Nat Chem ; 9(9): 843-849, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28837177

RESUMO

Berkelium (Bk) has been predicted to be the only transplutonium element able to exhibit both +III and +IV oxidation states in solution, but evidence of a stable oxidized Bk chelate has so far remained elusive. Here we describe the stabilization of the heaviest 4+ ion of the periodic table, under mild aqueous conditions, using a siderophore derivative. The resulting Bk(IV) complex exhibits luminescence via sensitization through an intramolecular antenna effect. This neutral Bk(IV) coordination compound is not sequestered by the protein siderocalin-a mammalian metal transporter-in contrast to the negatively charged species obtained with neighbouring trivalent actinides americium, curium and californium (Cf). The corresponding Cf(III)-ligand-protein ternary adduct was characterized by X-ray diffraction analysis. Combined with theoretical predictions, these data add significant insight to the field of transplutonium chemistry, and may lead to innovative Bk separation and purification processes.

3.
Dalton Trans ; 45(31): 12338-45, 2016 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-27424652

RESUMO

The divalent oxidation state is increasingly stable relative to the trivalent state for the later actinide elements, with californium the first actinide to exhibit divalent chemistry under moderate conditions. Although there is evidence for divalent Cf in solution and solid compounds, there are no reports of discrete complexes in which Cf(II) is coordinated by anionic ligands. Described here is the divalent Cf methanesulfinate coordination complex, Cf(II)(CH3SO2)3(-), prepared in the gas phase by reductive elimination of CH3SO2 from Cf(III)(CH3SO2)4(-). Comparison with synthesis of the corresponding Sm and Cm complexes reveals reduction of Cf(III) and Sm(III), and no evidence for reduction of Cm(III). This reflects the comparative 3+/2+ reduction potentials: Cf(3+) (-1.60 V) ≈ Sm(3+) (-1.55 V) ≫ Cm(3+) (-3.7 V). Association of O2 to the divalent complexes is attributed to formation of superoxides, with recovery of the trivalent oxidation state. The new gas-phase chemistry of californium, now the heaviest element to have been studied in this manner, provides evidence for Cf(II) coordination complexes and similar chemistry of Cf and Sm.

4.
Proc Natl Acad Sci U S A ; 112(33): 10342-7, 2015 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-26240330

RESUMO

Synthetic radionuclides, such as the transuranic actinides plutonium, americium, and curium, present severe health threats as contaminants, and understanding the scope of the biochemical interactions involved in actinide transport is instrumental in managing human contamination. Here we show that siderocalin, a mammalian siderophore-binding protein from the lipocalin family, specifically binds lanthanide and actinide complexes through molecular recognition of the ligands chelating the metal ions. Using crystallography, we structurally characterized the resulting siderocalin-transuranic actinide complexes, providing unprecedented insights into the biological coordination of heavy radioelements. In controlled in vitro assays, we found that intracellular plutonium uptake can occur through siderocalin-mediated endocytosis. We also demonstrated that siderocalin can act as a synergistic antenna to sensitize the luminescence of trivalent lanthanide and actinide ions in ternary protein-ligand complexes, dramatically increasing the brightness and efficiency of intramolecular energy transfer processes that give rise to metal luminescence. Our results identify siderocalin as a potential player in the biological trafficking of f elements, but through a secondary ligand-based metal sequestration mechanism. Beyond elucidating contamination pathways, this work is a starting point for the design of two-stage biomimetic platforms for photoluminescence, separation, and transport applications.


Assuntos
Elementos da Série Actinoide/química , Proteínas de Transporte/química , Proteínas de Transporte/fisiologia , Proteínas/química , Elementos da Série Actinoide/farmacocinética , Quelantes/química , Cristalografia por Raios X , Humanos , Concentração de Íons de Hidrogênio , Íons , Cinética , Elementos da Série dos Lantanídeos , Ligantes , Luminescência , Metais/química , Conformação Molecular , Centrais Nucleares , Fotoquímica , Ligação Proteica , Liberação Nociva de Radioativos , Espectrofotometria , Eletricidade Estática , Difração de Raios X
5.
Inorg Chem ; 54(7): 3462-8, 2015 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-25799124

RESUMO

The solution thermodynamics of the water-soluble complexes formed between 3,4,3-LI(1,2-HOPO) and Zr(IV) or Pu(IV) were investigated to establish the metal coordination properties of this octadentate chelating agent. Stability constants log ß110 = 43.1 ± 0.6 and 43.5 ± 0.7 were determined for [Zr(IV)(3,4,3-LI(1,2-HOPO))] and [Pu(IV)(3,4,3-LI(1,2-HOPO))], respectively, by spectrophotometric competition titrations against Ce(IV). Such high thermodynamic stabilities not only confirm the unparalleled Pu(IV) affinity of 3,4,3-LI(1,2-HOPO) as a decorporation agent but also corroborate the great potential of hydroxypyridinonate ligands as new (89)Zr-chelating platforms for immuno-PET applications. These experimental values are in excellent agreement with previous estimates and are discussed with respect to ionic radius and electronic configuration, in comparison with those of Ce(IV) and Th(IV). Furthermore, a liquid chromatography assay combined with mass spectrometric detection was developed to probe the separation of the neutral [M(IV)(3,4,3-LI(1,2-HOPO))] complex species (M = Zr, Ce, Th, and Pu), providing additional insight into the coordination differences between group IV and tetravalent f-block metals and on the role of d and f orbitals in bonding interactions.


Assuntos
Quelantes/química , Complexos de Coordenação/química , Plutônio/química , Piridonas/química , Compostos Radiofarmacêuticos/química , Zircônio/química , Estabilidade de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Ligantes , Estrutura Molecular , Termodinâmica
6.
J Pharm Biomed Anal ; 100: 157-166, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25165012

RESUMO

3,4,3-LI(1,2-HOPO) is a chelating ligand and decorporation agent that can remove radioactive lanthanides and actinides from the body. Identification of trace impurities in drug samples is gaining much interest due to their significant influence on drug activity. In this study, trace impurities were detected in manufactured lots of 3,4,3-LI(1,2-HOPO) by a developed method of liquid chromatography coupled with photo-diode array UV detection and electrospray ionization-quadrupole time of flight mass spectrometry (LC-QTOFMS), via induced-in-source or collision-induced mass fragmentation (nozzle-skimmer fragmentation). Molecular ions were fragmented within the nozzle-skimmer region of electrospray ionization (ESI) mass spectrometer equipped with a Time of Flight detector. Eight major (detected at levels higher than a 0.1% threshold) and seven minor trace impurities were identified. The respective structures of these impurities were elucidated via analysis of the generated fragment ions using mass fragmentation and elemental composition software. Proposed structures of impurities were further confirmed via isotopic modeling.


Assuntos
Quelantes/análise , Cromatografia Líquida/métodos , Contaminação de Medicamentos , Compostos Heterocíclicos com 1 Anel/análise , Piridonas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Tecnologia Farmacêutica/métodos , Modelos Moleculares , Estrutura Molecular , Software , Espectrofotometria Ultravioleta
7.
Chemistry ; 20(32): 9962-8, 2014 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-25043376

RESUMO

The photophysical properties, solution thermodynamics, and in vivo complex stabilities of Cm(III) complexes formed with multidentate hydroxypyridinonate ligands, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), are reported. Both chelators were investigated for their ability to act as antenna chromophores for Cm(III), leading to highly sensitized luminescence emission of the metal upon complexation, with long lifetimes (383 and 196 µs for 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), respectively) and remarkable quantum yields (45 % and 16 %, respectively) in aqueous solution. The bright emission peaks were used to probe the electronic structure of the 5f complexes and gain insight into ligand field effects; they were also exploited to determine the high (and proton-independent) stabilities of the corresponding Cm(III) complexes (log ß110 = 21.8(4) for 3,4,3-LI(1,2-HOPO) and log ß120 = 24.5(5) for 5-LIO(Me-3,2-HOPO)). The in vivo complex stability for both ligands was assessed by using (248) Cm as a tracer in a rodent model, which provided a direct comparison with the in vitro thermodynamic results and demonstrated the great potential of 3,4,3-LI(1,2-HOPO) as a therapeutic Cm(III) decontamination agent.


Assuntos
Quelantes/química , Cúrio/química , Substâncias Luminescentes/química , Piridonas/química , Poluentes Radioativos/química , Complexos de Coordenação/química , Cúrio/isolamento & purificação , Descontaminação , Luminescência , Poluentes Radioativos/isolamento & purificação , Termodinâmica
8.
Int J Radiat Biol ; 90(11): 1055-61, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24937372

RESUMO

PURPOSE: To characterize the dose-dependent and sex-related efficacy of the hydroxypyridinonate decorporation agent 3,4,3-LI(1,2-HOPO) at enhancing plutonium elimination when post-exposure treatment is delayed. MATERIALS AND METHODS: Six parenteral dose levels of 3,4,3-LI(1,2-HOPO) from 1-300 µmol/kg were evaluated for decorporating plutonium in female and male Swiss-Webster mice administered a soluble citrate complex of (238)Pu and treated 24 hours later. Necropsies were scheduled at four time-points (2, 4, 8, and 15 days post-contamination) for the female groups and at three time-points (2, 4, and 8 days post-contamination) for the male groups. RESULTS: Elimination enhancement was dose-dependent in the 1-100 µmol/kg dose range at all necropsy time-points, with some significant reductions in full body and tissue content for both female and male animals. The highest dose level resulted in slight toxicity, with a short recovery period, which delayed excretion of the radionuclide. CONCLUSIONS: While differences were noted between the female and male cohorts in efficacy range and recovery times, all groups displayed sustained dose-dependent (238)Pu elimination enhancement after delayed parenteral treatment with 3,4,3-LI(1,2-HOPO), the actinide decorporation agent under development.


Assuntos
Terapia por Quelação/métodos , Compostos Heterocíclicos com 1 Anel/química , Plutônio/efeitos adversos , Piridonas/química , Animais , Carga Corporal (Radioterapia) , Quelantes/química , Relação Dose-Resposta a Droga , Feminino , Rim/efeitos da radiação , Fígado/efeitos da radiação , Masculino , Camundongos , Plutônio/química , Piridonas/uso terapêutico , Fatores Sexuais , Fatores de Tempo
9.
Inorg Chem ; 52(15): 8805-11, 2013 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-23855806

RESUMO

The solution thermodynamics of water-soluble complexes formed between Ce(III), Ce(IV), Th(IV) and the octadentate chelating agent 3,4,3-LI(1,2-HOPO) were investigated. Several techniques including spectrofluorimetric and automated spectrophotometric titrations were used to overcome the slow spontaneous oxidation of Ce(III) complexes yielding to stability constants of log ß110 = 17.4 ± 0.5, log ß11-1 = 8.3 ± 0.4 and log ß111 = 21.2 ± 0.4 for [Ce(III)(3,4,3-LI(1,2-HOPO))](-), [Ce(III)(3,4,3-LI(1,2-HOPO)(OH)](2-), and [Ce(III)(3,4,3-LI(1,2-HOPO)H], respectively. Using the spectral properties of the hydroxypyridinonate chelator in ligand competition titrations against nitrilotriacetic acid, the stability constant log ß110 = 41.5 ± 0.5 was determined for [Ce(IV)(3,4,3-LI(1,2-HOPO))]. Finally, the extraordinarily stable complex [Ce(IV)(3,4,3-LI(1,2-HOPO))] was used in Th(IV) competition titrations, resulting in a stability constant of log ß110 = 40.1 ± 0.5 for [Th(IV)3,4,3-LI(1,2-HOPO))]. These experimental values are in excellent agreement with previous estimates, they are discussed with respect to the ionic radius and oxidation state of each cationic metal, and allow predictions on the stability of other actinide complexes including [U(IV)(3,4,3-LI(1,2-HOPO))], [Np(IV)(3,4,3-LI(1,2-HOPO))], and [Pu(IV)(3,4,3-LI(1,2-HOPO))]. Comparisons with the standard ligand diethylenetriamine pentaacetic acid (DTPA) provide a thermodynamic basis for the observed significantly higher efficacy of 3,4,3-LI(1,2-HOPO) as an in vivo actinide decorporation agent.


Assuntos
Cério/química , Quelantes/química , Compostos Organometálicos/química , Piridonas/química , Tório/química , Estabilidade de Medicamentos , Ligantes , Soluções , Termodinâmica
10.
Metallomics ; 5(6): 619-26, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23446908

RESUMO

Following an internal contamination event, the transport of actinide (An) and lanthanide (Ln) metal ions through the body is facilitated by endogenous ligands such as the human iron-transport protein transferrin (Tf). The recognition of resulting metallo-transferrin complexes (M2Tf) by the cognate transferrin receptor (TfR) is therefore a critical step for cellular uptake of these metal ions. A high performance liquid chromatography-based method has been used to probe the binding of M2Tf with TfR, yielding a direct measurement of the successive thermodynamic constants that correspond to the dissociation of TfR(M2Tf)2 and TfR(M2Tf) complexes for Fe(3+), Ga(3+), La(3+), Nd(3+), Gd(3+), Yb(3+), Lu(3+), (232)Th(4+), (238)UO2(2+), and (242)Pu(4+). Important features of this method are (i) its ability to distinguish both 1 : 1 and 1 : 2 complexes formed between the receptor and the metal-bound transferrin, and (ii) the requirement for very small amounts of each binding partner (<1 nmol of protein per assay). Consistent with previous reports, the strongest receptor affinity is found for Fe2Tf (Kd1 = 5 nM and Kd2 = 20 nM), while the lowest affinity was measured for Pu2Tf (Kd1 = 0.28 µM and Kd2 = 1.8 µM) binding to the TfR. Other toxic metal ions such as Th(IV) and U(VI), when bound to Tf, are well recognized by the TfR. Under the described experimental conditions, the relative stabilities of TfR:(MxTf)y adducts follow the order Fe(3+) >> Th(4+) ~ UO2(2+) ~ Cm(3+) > Ln(3+) ~ Ga(3+) >>> Yb(3+) ~ Pu(4+). This study substantiates a role for Tf in binding lanthanide fission products and actinides, and transporting them into cells by receptor-mediated endocytosis.


Assuntos
Elementos da Série Actinoide/metabolismo , Elementos da Série dos Lantanídeos/metabolismo , Receptores da Transferrina/metabolismo , Transferrina/metabolismo , Elementos da Série Actinoide/química , Transporte Biológico , Cromatografia Líquida de Alta Pressão , Elementos da Série dos Lantanídeos/química , Ligação Proteica , Transferrina/química
11.
J Am Chem Soc ; 135(7): 2676-83, 2013 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-23363005

RESUMO

Worldwide stocks of actinides and lanthanide fission products produced through conventional nuclear spent fuel are increasing continuously, resulting in a growing risk of environmental and human exposure to these toxic radioactive metal ions. Understanding the biomolecular pathways involved in mammalian uptake, transport and storage of these f-elements is crucial to the development of new decontamination strategies and could also be beneficial to the design of new containment and separation processes. To start unraveling these pathways, our approach takes advantage of the unique spectroscopic properties of trivalent curium. We clearly show that the human iron transporter transferrin acts as an antenna that sensitizes curium luminescence through intramolecular energy transfer. This behavior has been used to describe the coordination of curium within the two binding sites of the protein and to investigate the recognition of curium-transferrin complexes by the cognate transferrin receptor. In addition to providing the first protein-curium spectroscopic characterization, these studies prove that transferrin receptor-mediated endocytosis is a viable mechanism of intracellular entry for trivalent actinides such as curium and provide a new tool utilizing the specific luminescence of curium for the determination of other biological actinide transport mechanisms.


Assuntos
Elementos da Série Actinoide/química , Cúrio/química , Transferrina/química , Elementos da Série Actinoide/metabolismo , Cromatografia Líquida de Alta Pressão , Complexos de Coordenação/química , Cúrio/metabolismo , Humanos , Luminescência , Termodinâmica , Transferrina/metabolismo
12.
Dalton Trans ; 40(33): 8340-6, 2011 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-21766096

RESUMO

The spermine-based hydroxypyridonate octadentate chelator 3,4,3-LI(1,2-HOPO) was investigated for its ability to act as an antenna that sensitizes the emission of Sm(III), Eu(III), and Tb(III) in the Visible range (Φ(tot) = 0.2-7%) and the emission of Pr(III), Nd(III), Sm(III), and Yb(III) in the Near Infra-Red range, with decay times varying from 1.78 µs to 805 µs at room temperature. The particular luminescence spectroscopic properties of these lanthanide complexes formed with 3,4,3-LI(1,2-HOPO) were used to characterize their respective solution thermodynamic stabilities as well as those of the corresponding La(III), Gd(III), Dy(III), Ho(III), Er(III), Tm(III), and Lu(III) complexes. The remarkably high affinity of 3,4,3-LI(1,2-HOPO) for lanthanide metal ions and the resulting high complex stabilities (pM values ranging from 17.2 for La(III) to 23.1 for Yb(III)) constitute a necessary but not sufficient criterion to consider this octadentate ligand an optimal candidate for in vivo metal decorporation. The in vivo lanthanide complex stability and decorporation capacity of the ligand were assessed, using the radioactive isotope (152)Eu as a tracer in a rodent model, which provided a direct comparison with the in vitro thermodynamic results and demonstrated the great potential of 3,4,3-LI(1,2-HOPO) as a therapeutic metal chelating agent.


Assuntos
Quelantes/química , Európio/química , Európio/metabolismo , Compostos Organometálicos/química , Animais , Feminino , Camundongos , Soluções , Termodinâmica
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